{"entity": "researcher", "timestamp": "2026-08-22T06:57:26.886Z", "family": "Wingberm\u00fchle", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-5949-148X", "affiliations": ["Theoretical Chemistry, Ruhr University Bochum Bochum Germany sebastian.wingbermuehle@ruhr-uni-bochum.de."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/db393c4b5a774e2fb6b2d5063e3b530c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/db393c4b5a774e2fb6b2d5063e3b530c"}}, "publications": [{"entity": "publication", "iuid": "c53949e147464a73a5114e446417da57", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c53949e147464a73a5114e446417da57.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c53949e147464a73a5114e446417da57"}}, "title": "Partial peptide dissociation and binding groove plasticity in two major histocompatibility complex class I alleles - differences between alleles versus force field and sampling effects.", "authors": [{"family": "Wingberm\u00fchle", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-5949-148X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/db393c4b5a774e2fb6b2d5063e3b530c.json"}}, {"family": "Sch\u00e4fer", "given": "Lars V", "initials": "LV", "orcid": "0000-0002-8498-3061", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/623a14beaf724fc9a35be5042ec1a527.json"}}], "type": "journal article", "published": "2022-10-17", "journal": {"title": "RSC Adv.", "issn": "2046-2069", "volume": "12", "issue": "46", "pages": "29908-29914", "issn-l": "2046-2069"}, "abstract": "Major histocompatibility complex class I (MHC I) reports a cell's health status by presenting antigenic peptides inside its binding groove. However, MHC I binding grooves can differ largely in their plasticity, from binding grooves that are conformationally stable by themselves to those that require a high-affinity peptide to be bound to attain conformational stability. These latter MHC I alleles are dependent on the C-terminus of the peptide that stabilizes the F-pocket region of their binding grooves. It has remained unclear to what extent a peptide-MHC I complex (pMHC I) can tolerate the (intermittent) partial dissociation of high-affinity peptides, especially of the peptide's N-terminus. Using bias exchange umbrella sampling (BEUS), a technique to achieve enhanced sampling in molecular dynamics (MD) simulations, we obtained the free-energy profiles of the N-terminal dissociation of a respective high-affinity peptide from HLA-B*35:01 and HLA-B*44:02, two alleles on opposite ends of the scale regarding binding groove plasticity. The potential of mean force (PMF) for HLA-B*35:01 was calculated for two different sets of starting structures and is compared with a PMF obtained previously with a different force field to disentangle allele differences from force field and sampling effects. For both alleles, the free-energy profiles indicate that the peptide N-terminus dissociates in a substantial fraction of the pMHC I, suggesting that their crystal structures with fully bound peptides only partially capture the dynamic conformational ensemble of pMHC I in solution, and thus in the cell.", "doi": "10.1039/d2ra05324a", "pmid": "36321080", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9580618"}, {"db": "pii", "key": "d2ra05324a"}], "notes": [], "created": "2026-08-21T11:58:04.223Z", "modified": "2026-08-21T11:58:04.353Z"}]}